Full exome sequencing of 11 families with Hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is not a well-studied or easily treated disease. Genetic information is essential for advances in the understanding and treatment of HS. This study aims to examine mutations in the gamma-secretase complex, the Notch signalling pathway and to perform a Mendelian analysis of genetic variants that segregated with disease in a full exome sequencing of 11 families with HS. METHOD: Whole-exome sequencing and Mendelian analysis of 11 families with HS from Denmark. Patients with a clinical diagnosis of active HS and a positive family history of HS were recruited. Consenting family members were enrolled and examined for HS as well. We included 11 families, with a total of 51 participants, 24 with HS and 27 without. Whole-exome sequencing using HiSeq platform as paired-end 2 × 150 bases was used. RESULTS: We found mutations in the Notch pathway for all families. We found mutations in the PSENEN and APH1B of the gamma-secretase genes. We also report 161 variants of unknown significance that segregated with the disease within these families. CONCLUSIONS: We did not find causative mutation for each family in this study, supporting the theory that HS is rarely caused by single-gene mutations. We suggest that future genetic studies should be focused on genome-wide association with thousands of cases, as this technique is better suited for suspected polygenic diseases.

Randomized controlled trial of the tolerability, safety, and efficacy of adapalene gel 0.1% and tretinoin microsphere gel 0.1% for the treatment of acne vulgaris.

A prior meta-analysis of 5 randomized controlled trials indicates that adapalene gel 0.1% is as effective as tretinoin gel 0.025% against acne and has greater tolerability. To determine the tolerability and efficacy of adapalene gel 0.1% versus tretinoin microsphere gel 0.1% in 168 patients with acne vulgaris, we conducted a 12-week, multicenter, randomized, controlled, investigator-masked, parallel-group design study. Efficacy variables included noninflammatory, inflammatory, and total lesion counts; global grade; and global assessment of improvement in acne severity. Skin tolerability variables included erythema, desquamation (scaling), dryness, pruritus, and stinging/burning. Our results showed that the efficacy of adapalene gel 0.1% was comparable to that of tretinoin microsphere gel, and both treatments had similar onset of action. Cutaneous tolerability was noted in both groups, with scores significantly better with adapalene gel 0.1% than with tretinoin microsphere gel 0.1%, and significantly fewer treatment-related adverse events were reported with adapalene gel 0.1%.

Comparison of adapalene 0.1% solution and tretinoin 0.025% gel in the topical treatment of acne vulgaris.

A multicentre study was conducted to compare clinical safety and efficacy of adapalene 0.1% solution and tretinoin 0.025% gel, both topical treatments for acne, in a once-daily dosage regimen for 12 weeks. A total of 297 patients were enrolled by eight investigators in this randomized, investigator-masked study in a parallel group design. An open label period using adapalene followed this study to assess the long-term safety of adapalene solution. Adapalene and tretinoin proved to be clinically and statistically effective in treating acne by reducing inflammatory (47% and 50%, respectively) and non-inflammatory lesions (57% and 54%) as compared to baseline. When comparing patients who had 75% or greater improvement in open comedones, adapalene was shown to be significantly more effective than tretinoin. No serious adverse event was reported during this study, including during the long-term period. The reactions that occurred were similar between treatments, i.e. burning, pruritus, scaling, dryness and erythema.

A comparison of the efficacy and tolerability of adapalene 0.1% gel versus tretinoin 0.025% gel in patients with acne vulgaris: a meta-analysis of five randomized trials.

The purpose of this meta-analysis was to determine if adapalene 0.1% gel (Differin) provided superior efficacy and better tolerability than tretinoin 0.025% gel in the treatment of acne vulgaris. All comparative studies, both published and unpublished, from the United States and Europe, that fulfilled rigorous protocol criteria (multicentre, randomized, investigator-blind) were used. Five comparative studies met these criteria. In total, the meta-analysis evaluated 900 patients (450 treated with adapalene 0.1% gel, 450 treated with tretinoin 0.025% gel) with mild-to-moderate acne from the combined clinical trials. To avoid study bias, the meta-analysis used an intention-to-treat analysis. Statistical methodology for the meta-analysis included analysis of covariance, analysis of variance and Cochran-Mantel-Haenszel test. All statistical tests were two-sided, with the 0.05 probability level used to establish statistical significance, and 95% confidence intervals used to assess equivalence. Adapalene demonstrated equivalent efficacy to tretinoin in terms of reducing total lesion count. Adapalene demonstrated more rapid efficacy, as evidenced by a significant difference in the reduction of inflammatory and total lesions at week 1. Adapalene also demonstrated considerably greater local tolerability at all evaluation periods. The findings from this meta-analysis suggest that adapalene 0.1% gel constitutes a pharmacologic advance over such classic retinoids as tretinoin for the treatment of acne vulgaris.

[Exogenous photosensitizing agents]. / Agents photosensibilisants exogènes.

The frequent use of remedies either in topical or systemic form has led to a rising number of photosensitizations. The different cutaneous manifestations of exogenous photosensitizers e.g. phototoxicity and photoallergy, are described. We treat the most important agents of these reactions and lay stress upon the patient's interview and the phototesting in order to find out the substance, that induced photodermatosis.

Variation in 8-methoxypsoralen profiles during long-term psoralen plus ultraviolet A therapy and correlations between serum 8-methoxypsoralen levels and chromametric parameters.

Three serum 8-methoxypsoralen (8-MOP) kinetics tests were performed on 15 patients undergoing PUVA therapy. The first test was carried out before beginning PUVA treatment, the 2nd one at the 10th session and the 3rd test at the 20th PUVA session. Blood samples were taken every 30 min after the drug was taken and a standard meal ingestion during 3 h to determine the serum 8-MOP peak level and corresponding time. For 14 patients, UVA-induced erythema was measured with a Minolta CR 200 chromameter, 3 (before beginning PUVA treatment, just before 10th session and 48 h later) or 5 times (before beginning PUVA treatment, just before 10th session and 48 h later, just before 20th session and 48 h later). There was a wider distribution of serum 8-MOP peak levels in the 3rd test than in 2nd one and in the 2nd one than in the first one. These facts suggest a heterogeneity in 8-MOP metabolism in the 15 patients: 11 patients showed an earlier serum 8-MOP peak and an earlier appearance of the drug in blood in the 3rd and 2nd test than in the first one. For 9 of these 11 patients, serum 8-MOP peak levels were higher and higher from the first profile to the 3rd one, suggesting an inhibition of 8-MOP metabolism in time. In the remaining 4 patients, the 8-MOP peak time and the appearance of the drug in blood were delayed in the 3rd test compared with the first profile.(ABSTRACT TRUNCATED AT 250 WORDS)